Cholesterol How To Lower

Lower Cholesterol By Scott Davis

In Beat Cholesterol in 30 Days, Scott Davis, a medical researcher and expert in alternative health (also a former sufferer of cholesterol), lets out his studies-based discoveries for beating high cholesterol levels with no drugs, no dangers involved, and no side effects to worry about. This program reveals to people some main factors that cause their hypercholesterolemia such as smoking, high blood pressure, diabetes, obesity, and family history of heart disease. The program also covers tips to prevent the recurrence of hypercholesterolemia such as eating a low-fat and low-salt diet, stopping smoking, losing extra pounds, and maintaining a healthy weight. It includes simple dieting tips that naturally reduce cholesterol, superfoods that will reduce cholesterol quickly, and much more. As you go through the e-book, you discover facts about foods and exercise that are often simple but life-changing (such as how to maximize results from your workouts to get better results from less exercise) as well as disturbing truths about the less-considered dangers of many prescription medications. Read more...

Natural Cholesterol Guide Summary

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My Natural Cholesterol Guide Review

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I've really worked on the chapters in this book and can only say that if you put in the time you will never revert back to your old methods.

All the modules inside this e-book are very detailed and explanatory, there is nothing as comprehensive as this guide.

Hypercholesterolemia Statins

Hypercholesterolemia contributes significantly to overall cardiovascular morbidity and mortality. Statins are the number one class of anticholesterol medications. They are well known for side effects of gastrointestinal disturbance, headache, and rash. For athletes, myalgias and, rarely, rhabdomyolysis are possible complications of significant import. Baseline creatine kinase levels prior to onset of statin therapy may be useful in case these complications arise.15 Most changes in creatine kinase levels with statin use and or exercise are asymptomatic. Rhabdomyolysis appears to be more likely to occur due to a combination of statin use, exercise, and another medication metabolized by cytochrome P-450.16 In an experimental trial of over-the-counter use of statins, 17 of users experienced a drug-related adverse event, and 12 of users discontinued statin therapy due to an adverse event.17 Most studies of statins and exercise involve patients with some form of vascular disease. In...

Raising High Density Lipoprotein Cholesterol Levels

Fibrates, which are agonists of the PPAR-a receptor, increase the hepatic production of apolipoprotein A-I, which is the principal lipoprotein contained in the HDL particle and that raises HDL levels by approximately 10 to 15 (although others have shown almost no effect). Niacin reduces the hepatic clearance of the mature HDL particle, raising circulating HDL-C levels by 20 to 30 . Cholesterol estertransfer protein (CETP) is a plasma glycoprotein that facilitates the transfer of cholesteryl esters from HDLC to apoB-containing lipoproteins and triglycerides from apoB-containing lipoproteins to HDL. Increasing the triglyceride content of HDL increases its clearance, thereby reducing HDL-C levels.

Your HDL Cholesterol Level

HDL cholesterol is the good type in fact, it's the only good kind of cholesterol. Some folks are genetically blessed with high HDL readings, a lucky inherited gene which significantly reduces the risk for heart disease. Other folks have to work at elevating their numbers. Smoking, being overweight, and being sedentary can all result in lower HDL cholesterol. If you learn that you have low HDL cholesterol, you can help raise it by not smoking, by losing weight or maintaining a healthy weight, adding monounsaturated fat to your diet (olives, nuts and avocado), and by being physically active for at least 30-60 minutes a day. Desirable HDL cholesterol levels are 40 mg dL or higher. People with high blood triglycerides usually have lower HDL cholesterol and a higher risk of heart attack and, indirectly, of stroke. Furthermore, many people with high triglycerides have underlying diseases or genetic disorders. If this applies to you, the main therapy is to change your lifestyle by...

Autosomal Recessive Hypercholesterolemia Is Due To Defects In Ldlrmediated Endocytosis

Khachadurian described the first of these disorders, known as autosomal recessive hypercholesterolemia (ARH), which is a phenocopy of FH (Khachadurian and Uthman 1973). The index cases were four Lebanese siblings who had the clinical features of homozygous FH, including severe hypercholesterolemia (mean plasma cholesterol level of 728 mg dl), huge tendon xanthomas, and premature CAD, but only a modest reduction in LDLR activity in cultured fibroblasts. The parents of the four siblings were normo-cholesterolemic (Khachadurian and Uthman 1973). Subsequently, additional subjects with an autosomal recessive form of hypercholesterolemia who had normal LDLR function in their fibroblasts were described (Harada-Shiba et al. 1992 Zuliani et al. 1995, 1999 Schmidt et al. 1998), including five families from Sardinia (Zuliani et al. 1995, 1999). LDL turnover studies performed in two of the Sardinian probands revealed a fourfold reduction in the rate of clearance of...

Oxidative Stress in Hypercholesterolemia Associated ED

Hypercholesterolemia is a significant risk factor for ED attributed to both vasculo-genic and neurogenic factors, although the molecular mechanisms of the latter are largely unknown. Increased oxidative stress has been postulated to be major molecular factors contributing to hypercholesterolemia-induced vasculogenic ED 72-74 . Corpus caver-nosal tissue of cholesterol-fed animals exhibits increased production of ROS 75-79 . In the mouse penis, hypercholesterolemia increases protein expressions of NADPH oxidase subunits p67p hox, p47phox. and gp91p hox 76 , while inhibition of NADPH oxidase by diphenyleneiodonium chloride and apocynin inhibits ROS production and preserves erectile function 76, 77 . These findings indicate a crucial role for NADPH oxidase as a ROS-producing enzyme in ED associated with hyper-cholesterolemia. In addition to NADPH oxidase, eNOS uncoupling 75, 76 , but not xanthine oxidase 77 , also serves as a source of ROS in the penis of experimental hypercholesterolemic...

Statins HMGCoA Reductase Inhibitors

Statins are very effective LDL-lowering medications and are proven to reduce the risk of CHD, stroke, and death. Thus, NCEP ATP III considers statins the preferred LDL-lowering medications. Data concerning the efficacy and safety of the statins now go back nearly 25 years. Statins are effective in reducing MIs, strokes, revascularization procedures, cardiovascular deaths, and in some cases, total mortality. This effectiveness has been demonstrated in both genders, the elderly, patients with diabetes and hypertension, those with and without pre-existing CHD, and following an acute coronary syndrome.14-25 Statins inhibit conversion of HMG-CoA to L-mevalonic acid and subsequently cholesterol. Statins lower LDL cholesterol levels by approximately 25 to 62 (Table 12-8). A substantial reduction in LDL cholesterol occurs at the usual starting dose and each doubling of the daily dose only produces an additional 6 average reduction (known as the rule of 6). This is important when considering...

Pharmacologic Interventions Statins

Knee Plica Exercises

The statins are reversible, competitive 3-hydroxy-3-meth-ylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. HMG-CoA reductase is the rate-limiting step for cholesterol biosynthesis in the liver and systemic tissues. Statins are the most potent agents for reducing serum levels of LDL-C. The statins augment the elimination of atherogenic apoB100-con-taining lipoproteins (VLDL, VLDL remnants, and LDL) from plasma by upregulating the LDL receptor on the surface of hepatocytes. The statins also reduce VLDL secretion and stimulate apoprotein-AI expression and hepatic HDL secretion. Many prospective, placebo-controlled clinical trials have shown that the statins significantly reduce rates of MI, stroke, and coronary and all-cause mortality in the primary prevention (Downs et al., 1998) and secondary prevention settings (Scandinavian Simvastatin Survival Study Group, 1994). Statins reduce the frequency of stable and unstable angina and decrease atheromatous plaque progression and, based on...

Statins

Ciates, in a case-control study involving patients who underwent major vascular surgery at a single center, noted an independent, greater than fourfold reduction in perioperative mortality among patients receiving statins at the time of surgery.24 In another analysis of patients who underwent open abdominal aortic aneurysm repair, statin use was associated with significant reductions in adjusted 30-day death or MI (3.7 vs. 11.0 ), in late (median, 4.7 years) all-cause mortality (18 vs. 50 ), and in cardiac mortality (11 vs. 34 ).25 These provocative findings require confirmation in a randomized controlled trial before firm treatment recommendations are possible. However, most patients undergoing vascular surgery already possess indications for chronic statin therapy for the prevention of cardiac events, and among patients already receiving treatment it seems reasonable to continue statin therapy through the perioperative course. Potential mechanisms by which statins may reduce...

High Cholesterol

Cholesterol levels are affected by diet. Diets rich in vegetables and fruits and even including moderate amounts of alcohol have been shown to help prevent heart disease. 200 milligrams per deciliter (mg dl) of blood. Studies of large groups of people have shown that when a person's cholesterol level is more than 240 mg dl, the risk of heart attack is double that of those people with a cholesterol level less than 200 mg dl. What is an acceptable cholesterol level may actually vary from one person to another. For example, when a person has no risk factors for cardiovascular disease is not obese, is not diabetic, is a nonsmoker, and has no family history of heart disease the doctor may be comfortable in regularly reevaluating such a patient with a cholesterol level in the 240 mg dl range without prescribing cholesterol-lowering medication. On the other hand, when a patient has numerous risk factors or known atherosclerotic heart disease, a doctor will work with the patient to decrease...

Triglycerides

Hypertriglyceridemia is a strong predictor of CHD. Prospective studies such as the Multiple Risk Factor Intervention Trial (MRFIT) show that the adjusted risk of a fatal or nonfatal CHD event is greater among subjects with triglyceride levels of 200 mg dL or higher. This was the result regardless of whether the subjects were in a fasting or nonfasting state. The Whitehall II study showed the potential relevance of combining triglycerides and cholesterol in risk prediction. There is also an inverse relationship between serum levels of HDL-C and triglycerides, with low serum HDL-C levels representing an independent risk factor for cardiovascular disease and the so-called atherogenic lipid triad, consisting of high serum triglyceride levels, low serum HDL-C levels, and a preponderance of small, dense, LDL-C particles. This feature is particularly common in obesity and insulin-resistant states. More than 2.5 million deaths each year worldwide are weight related, with cardiovascular...

Inflammation And Percutaneous Coronary Intervention

The treatment of stable yet symptomatic coronary atherosclerosis and unstable coronary atherothrom-bosis has progressed from balloon angioplasty to the modern era of DES and will continue to evolve. Adjunctive medical therapy in the form of statins, glycoprotein inhibitors, and thienopyridines and antithrombin agents has also been a mainstay of treatment aimed at controlling risk factors and progression of disease, both at the time of intervention and afterward. The ultimate success or failure of PCI and management of coronary atherosclerosis varies among individuals. Beyond technical considerations, revascularization has been and will continue to be limited in efficacy by one major variable inflammation. The focus of treatment must address inflammation to improve outcomes in PCI.

Statin Therapy HMGCoA Reductase Inhibitors

The use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in ACS and coronary atherosclerosis has illuminated the role of the potential nonlipid effects of these drugs. Statin therapy is thought to affect inflammatory processes contributing to atherosclerosis. Specifically, statins produce pleiotropic effects by actions on isoprenoids. By inhibiting the production of isoprenoids, statins interfere with G protein-mediated upregula-tion of transcription factors responsible for inflammatory signaling.57 Statins can affect numerous pathways that contribute to inflammation, including adhesion molecules, cytokines, and a variety of inflammatory cell types. A reduction in the levels of ICAM-1 CD54 and CD18 CD11a by statins has been shown to occur through reduction of messenger RNA (mRNA) transcript.58 Statins have the ability to downregulate leukocyte mRNA for various cytokines such as IL-6, IL-8, and MCP-1. Statins also affect the balance of helper T...

Clinical Examples Of The Anatomic Paradigm In Practice

The results of randomized trials do not necessarily apply in the same way if either the control (standard) therapy or the active therapy has undergone major improvement since completion of the trial. With highly significant improvements in survival resulting from the use of aspirin, statins, P-blockers, and ACE inhibitors ARBs, the likely long-term mortality of medical therapy arms in 2008 is substantially better than it was in the 1960s, when medical therapy was compared with CABG. Although CABG has also improved since the 1960s, there is no body of large randomized trials showing superiority of current techniques to those of 40 years ago. For example, although it is believed that routine use of the left internal mammary or thoracic artery as a conduit is an important clinical advance, there is not one randomized trial comparing use of the internal mammary artery with saphenous vein graft implantation into the same recipient vessels, under the same conditions, with the same adjuncts...

Burden of Disease

Of U.S. adults, 16 have a total cholesterol level greater than 240 mg dL. Women have a higher prevalence of elevated total cholesterol than men (Schober et al., 2007). Low HDL is much more common in men than women (AHA, 2005). Total cholesterol levels higher than 200 mg dL account for 27 of coronary heart disease (CHD) events in men and 34 in women. Elevated total cholesterol and low-density HDL cholesterol mg dL

Combination Therapy for Elevated LDL Cholesterol

For patients who don't achieve their LDL or non-HDL cholesterol goals with statin monotherapy and lifestyle modifications including those unable to tolerate high doses due to adverse effects, combination therapy may be appropriate. Resins or ezetimibe combine effectively with statins to augment LDL cholesterol reduction. When added to a statin, ezetimibe can reduce LDL cholesterol levels by an additional 18 to 21 or up to 65 total reduction with maximum doses of the more potent statins. Ezetim-ibe and simvastatin are available as a combination tablet (Vytorin) and indicated as adjunctive therapy to diet for the reduction of elevated total cholesterol, LDL cholesterol, Apo B, triglycerides, and non-HDL cholesterol, and to increase HDL cholesterol. The usual starting dose is 10 mg 20 mg, and the maximum dose is 10 mg 80 mg (Table 12-9). Adverse events are similar to those of each product taken separately however, the percentage of patients with LFT elevations greater than three times...

General Considerations

There has been an increasing interest throughout the world in the use of natural ingredients for health, especially tea. Tea is the world's second most popular beverage after water. Green tea accounts for approximately 20 of all tea consumed. It has been claimed that overall health of the body, especially the oral cavity, can be maintained by the consumption of green tea. Green tea is not fermented therefore, it contains polyphenols that are inactivated in the fermentation process of black tea production. Green tea has been consumed in East Asia, where its benefits have been claimed for centuries. Green tea polyphenols possess antioxidant and antiviral properties that account for its benefits these benefits have been touted to include lowering blood pressure, lowering cholesterol, stabilizing blood glucose, inhibiting bacterial growth, and blocking many carcinogenic agents. Polyphenols have been shown to inhibit the growth of Streptococcus mutans, the major etiologic bacterium...

Dont Be Fooled by Misleading Labels

How does saturated fat work its way into the cholesterol picture This artery-clogging culprit can also raise blood cholesterol levels. Just imagine how harmful the high-fat animal foods such as marbled red meats and whole milk dairy products can be they contain both saturated fat and cholesterol.

National Cholesterol Education Program Recommendations

Dextrothyroxine, clofibrate, and niacin on recurrent disease in men. Clofibrate resulted in an 8 reduction in total cholesterol and a 25 reduction in triglycerides but no significant reduction on the combined end point of cardiac death and nonfatal MI at 5 years.8 Subjects who were assigned to niacin treatment achieved a 10 reduction in total cholesterol and a 25 reduction in triglyceride levels. At 5 years, a dose of niacin (3 g day) was associated with a significant reduction in CHD death or MI (25.6 versus 30.1 , P < .005).9 Benefit was not evident after the second year of therapy. The Stockholm Ischaemic Heart Disease Prevention study evaluated the combination of niacin (3 g day) and clofibrate (2 g day).10 Total mortality and, notably, CHD mortality were significantly reduced in the lipid-lowering therapy group (16.8 and 21.9 versus the control group rates of 26.4 and 29.7 , P < .05 and P < .01, respectively). A significant reduction in nonfatal MI was reported at 44 months...

Early Secondary Prevention Statin Trials

During a decade of clinical research, successive trials using statins have demonstrated the benefit of lowering serum cholesterol in a wide range of clinical conditions compared with diet alone. The first of these trials was the Scandinavian Simvastatin Survival Study (4S) trial, which randomized 4444 patients with angina pectoris or previous MI and serum cholesterol levels of 215 to 312 mg dL (5.5 to 8.0 mmol L) Cholestyramine LDL-C, low-density-lipoprotein cholesterol TC, total cholesterol TG, triglycerides. LDL-C, low-density-lipoprotein cholesterol TC, total cholesterol TG, triglycerides. with consistent findings, demonstrating a reduction in major coronary events with pravastatin (40 mg) versus placebo, as well as reductions in the rates of revascularization and stroke in patients with normal cholesterol levels.14 The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial was the largest of the three early secondary prevention trials (N 9014 patients), and it...

Heart Protection Study And Cholesterol Treatment Trial Metaanalysis

CTT collaboration effects on major coronary events per mmol L LDL cholesterol reduction subdivided by baseline lipid values HDL cholesterol Triglycerides Figure 11-3. The relationship between baseline lipid levels and the benefit of statin therapy was shown in the Cholesterol Treatment Trial (CTT) meta-analysis. The effects of major coronary events per 1 mmol L of low-density lipoprotein (LDL) cholesterol reduction subdivided by baseline lipid values are shown. (Modified from Baigent C, Keech A, Kearney PM, et al Efficacy and safety of cholesterol-lowering treatment Prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005 366 1267-1278.) The early trials looking at treatment of acute coronary syndrome (ACS) (i.e., 4S, CARE, and LIPID) excluded patients within the first 4- to 6-month period after ACS. The Myocardial Ischemia Reduction with Acute Cholesterol Lowering (MIRACL) trial provided the first evidence that statin therapy...

Intensive Statin Therapy For Acute Coronary Syndrome

The TNT trial compared a strategy of intensive lipid lowering using 80 mg of atorvastatin with 10 mg of atorvastatin in patients with stable CHD in 10,001 patients over 5.5 years. The definition of CHD in the study population included patients with previous MI, those with stable angina with objective evidence of atherosclerotic CHD, or patients who had undergone revascularization. After an open-label run-in phase with 10 mg of atorvastatin for 8 weeks, patients were randomized to 10 or 80 mg of atorvastatin (i.e., double-blind period). The primary end point of TNT was the time to occurrence of a major cardiovascular event, defined as CHD death, nonfatal MI, resuscitated cardiac arrest, and fatal or nonfatal stroke. During the open-label phase, LDL-C levels fell from 152 mg dL (3.9 mmol L) to a mean of 98 mg dL (2.6 mmol L). Among those randomized to 80 mg of atorvastatin after the open-label phase, LDL-C fell further by 21.4 to a mean of 77 mg dL (2 mmol L). A significant further...

Intensive Statin Therapy And Atherosclerosis

Given the clinical impact of statin therapy of cardiovascular event reduction in patients with CAD, it is intuitive to expect that statins would reverse atherosclerosis disease burden. Several trials used angiogra-phy to assess the impact of standard-dose statin therapy on the extent of angiographic disease. Although standard doses of statins reduced LDL-C levels by 20 to 30 , they failed to demonstrate regression of disease burden, but instead consistently showed that in the presence of CAD, statins reduce the rate of progression of disease.34

Reduction in CReactive Protein Levels

Statins possess pleiotropic effects that are mediated by HMG-CoA reductase but are not dependent on lowering of LDL-C levels (Fig. 11-11). All statins lower CRP levels, in part related to the statin dose. In PROVE IT, the median levels of CRP were similar in the 80-mg atorvastatin and 40-mg pravastatin groups (12.2 and 11.9 mg L, respectively P .60) at study entry, but they were significantly lower in the ator-vastatin group than in the pravastatin group at 30 days (1.6 versus 2.3 mg L, P < .001), 4 months (1.3 versus 2.1 mg L, P < .001), and the end of the study (1.3 versus 2.1 mg L, P < .001). Although the levels of LDL-C and CRP were reduced by statin therapy at Figure 11-11. Inhibition of HMG-CoA reductase leads to low-density lipoprotein cholesterol (LDL-C)-mediated effects through the liver and nonlipid-related effects in the vessel wall. (From Ray KK, Cannon CP The potential relevance of the multiple lipid-independent (pleiotropic) effects of statins in the management of...

Cholesterol Ester Transfer Protein Inhibition

The reverse cholesterol transport pathway of high-density lipoprotein (HDL). Lipid-poor pre-P-HDL cholesterol, rich in apolipoprotein A-I (apoA-I), is synthesized by the liver or intestinal mucosa and released into the circulation, where it promotes the transfer of excess cellular-free cholesterol (FC) from macrophages to apoA-I by interacting with the ATP-binding cassette transporter A1 (ABCA1) in arterial wall macrophages. Plasma lecithin-cholesterol acyltransferase (LCAT) converts free cholesterol in pre-P-HDL cholesterol to cholesteryl ester (CE), resulting in the maturation of pre-P-HDL cholesterol to mature a-HDL cholesterol. The a-HDL cholesterol is transported to the liver by a direct or indirect pathway. In the direct pathway, selective uptake of cholesteryl ester by hepatocytes occurs with the scavenger receptor, class B, type 1 (SR-B1). In the indirect pathway, HDL cholesterol cholesteryl ester is exchanged for triglycerides in apolipoprotein B-rich particles...

Vitamin D The Sunshine Vitamin

On the other hand, vitamin D is fat soluble, so taking large supplemental doses can be dangerous. Some of the toxic effects involve drowsiness, diarrhea, loss of appetite, headaches, high blood pressure, high cholesterol, fragile bones, and calcium deposits throughout your body (including your heart, kidneys, and blood vessels). If you are taking supplements, make sure you're not getting much more than the recommended amount for your age category you'll notice that folks over 50 need more. Also, note that the adequate intake (AI) for vitamin D is given in micrograms on the chart the vitamin D in food and supplements is usually measured in international units (TU). The conversion is one microgram 40 international units (IU).

Beta Adrenergic Receptor Blockers

Tive heart failure), these differences mainly affect side effects, contraindications, and frequency of dosing. For example, nonselective agents may increase bron-chospasm in asthmatic patients. Lipophilic agents may have more central nervous system effects, such as sedation and depression. The type of metabolism affects plasma half-life in patients with renal or hepatic insufficiency. P-Blockers with ISA slow the heart rate less than P-blockers without ISA P-blockers with ISA are less likely to decrease HDL or increase triglycerides.

Research Evidence to Date

The third component of macrobiotic research concerns specific products or ingredients. Although no food products cure disease, the preventive benefits of some diets through puberty are well documented. Healthy diets may be an explanation for Asian women's lower rates of breast and other cancers compared to those of American women. Soy versus animal protein has been shown in scientific studies to decrease cholesterol. The lower fat intake through puberty associated with dietary soy products may help decrease the incidence of breast cancer.

Common risk factors and prevention

The aim of primary prevention is to reduce the risk of first-ever stroke in asymptomatic people. Seven factors are regarded as potentially modifiable risk factors for vascular diseases high blood pressure, high cholesterol, smoking, excessive or heavy regular alcohol consumption, physical inactivity, overweight and dietary factors. The strategy in primary prevention is to lower stroke risk attributed to these factors through education, lifestyle changes and medication. Non-modifiable risk factors arising from diseases such as atrial fibrillation or diabetes mellitus can be lowered by controlling and treating the underlying disorder. Targets of primary stroke prevention can be the entire population or high-risk - but stroke-free - individuals partly suffering from disorders such as hypertension or diabetes mellitus.

Risk factor socioeconomic status

Percentage of people aged 18 to 74 years with high levels of physical inactivity and high cholesterol, by educational level, age standardized 1986-1992 men women physical inactivity high cholesterol physical inactivity high cholesterol physical inactivity high cholesterol Risk factors for CVD are similar for men and women, but tobacco use is more dangerous in women. In addition, high blood triglycerides are an important cause of atherosclerosis in young women, but not in young men. The menopause has no direct effect, but hormone replacement therapy increases the risk of CVD.

Impact of Statin Therapy

The inflammatory response of distal embolization and platelet aggregate interaction with leucocytes contributes to the degree of myonecrosis that is frequently seen after PCI. The observations made in PCI registries demonstrated a reduction in PMI in patients who have been receiving statins at the time of their PCI.67 Proposed mechanisms that can explain this finding include an anti-inflammatory effect and the ability of statins to enhance nitric oxide produc-tion.68 In an analysis of 803 patients undergoing rota A subgroup analysis of the ARMYDA trial confirms the anti-inflammatory role of statins in reducing myonecrosis post-PCI. In 138 patients, serum levels of adhesion molecules (e.g., ICAM, VCAM, E-selectin) were similar in patients in the atorvastatin group and the placebo group before PCI. However, after PCI, the rise in the levels of ICAM and E-selectin was significantly attenuated with atorvastatin therapy. This attenuated rise in adhesion molecules paralleled the protective...

Variation in the estrogen receptor

These rare experiments of nature suggest that estrogens are important in maintaining normal carbohydrate and lipid metabolism as well as normal endothelial-dependent nitric oxide mediated vasodilatation in men. They are compatible with data from transgenic knockout models confirming that estrogen receptor a is important in preventing adipocyte hypertrophy, obesity, insulin resistance and hypercholesterolaemia (Heine etal. 2000) and maintaining basal nitric oxide release from vascular endothelium in male animals. Estrogen receptor (p in vascular smooth muscle may also regulate vascular sensitivity to estradiol (Hodges etal. 2000 Nilsson et al. 2000 Rubanyi et al. 1997). The favourable effects of estrogens on HDL-C demonstrated are also in accord with clinical studies using aromatase inhibitors in normal men. Several polymorphisms of intronic sequences of the estrogen receptor a gene which are in linkage dysequilibrium with each other were previously found to modulate the response of...

Lipoprotein Metabolism

Discrepant findings on lipoprotein metabolism in PHPT include increased and decreased levels of serum triglycerides, decreased serum cholesterol, increased serum very-low-density-lipoproteins (VLDL), and no changes at all.121124 Hagstrom and colleagues125 found decreased high-density-lipoprotein (HDL) cholesterol, increased total triglycerides, and VLDL cholesterol, and an elevated atherogenic index in patients with mild PHPT. Parathyroidectomy normalized the dyslipidemia within 1 year. Five-year surveillance of PHPT patients without treatment was found to be associated with a maintained increase in total triglycerides and the atherogenic index and a decrease in HDL cholesterol levels. These findings favor operative intervention rather than conservative surveillance, even in patients with asymptomatic, mild PHPT. It has also been reported that increased PTH levels both in vivo and in vitro increase lipolysis, perhaps causing the elevated VLDL levels.126,127 In a further study,...

Cardiovascular Risk Factors

(From Banerji MA, Buckley MC, Chaiken RL, et al. Liver fat, serum triglycerides and visceral adipose tissue in insulin-sensitive and insulin-resistant black men with NDDM. Int J Obes 1995 19 846-850) (From Banerji MA, Buckley MC, Chaiken RL, et al. Liver fat, serum triglycerides and visceral adipose tissue in insulin-sensitive and insulin-resistant black men with NDDM. Int J Obes 1995 19 846-850) Insulin resistance and increased visceral adiposity in the setting of metabolic syndrome are associated with changes in multiple risk factors (Lamon-Fava et al., 1996) (Fig. 27-6). Insulin-resistant adipose tissue is a potent source of angio-tensinogen, the precursor to vasoconstrictor angiotensin II. The BP in these patients also increases because (1) insulin stimulates increased sodium reabsorption at the level of the proximal tubular epithelium, which increases intravascular volume (2) there is reduced endothelial nitric oxide production (Caballero, 2003) and (3) there is increased...

Heart Related Diseases

Studies have clearly demonstrated a consistently positive relationship between increased serum cholesterol level in the form of low density lipoprotein and the rate of heart disease. At high levels the association is particularly strong. Good evidence exists that lowering cholesterol levels with drug therapy will lower death rates from coronary disease. Exercise, too, has a beneficial effect on the types of lipids circulating in the bloodstream.

Trials Of Pharmacologic Agents

The next large lipid-lowering trial was the Lipid Research Clinics Coronary Primary Prevention Trial.10 This trial compared cholestyramine resin versus placebo to see if there would be a difference in the primary outcome of coronary heart disease death or non-fatal myocardial infarction in 3806 men free of prior evidence of heart disease, but with hyperlipoproteinaemia. There were 155 events in the intervention group and 187 in the placebo group (one-sided p < 0.05). This study was one of the first to show benefits from lipid lowering, even though some questioned the significance of the results, given the one-sided test. More definitive outcomes from cholesterol lowering had to wait for the development of agents that were more effective in lowering lipids and, importantly, better tolerated. The clinical trials of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ('statins') were primarily conducted in the 1990s. Trials such as the Scandinavian Simvastatin Survival...

Trials Of Behaviour Change

Smoking prevention or cessation diet change for weight loss, blood pressure reduction or cholesterol reduction and exercise for risk factor reduction and better outcomes in people with a heart attack or heart failure. enough magnitude to alter mortality. This is what happened in some of the early trials of cholesterol lowering that failed to show improvement in mortality. The early lipid-lowering drugs were not as effective as the current ones in reducing cholesterol. Third, the measures of depression and social support, particularly when obtained shortly after a major event such as a heart attack, might not reflect true 'baseline'. Fourth, however, even though mortality and recurrent infarction were unchanged, the apparent improvements in depression and social support are not trivial findings. Unlike surrogate outcome variables that have little clinical meaning, these outcomes are clinically important in their own right.

Laboratory Abnormalities

The confirming tests for lupus (e.g., ANA, anti-DNA titers) are generally not helpful in follow-up. Monitoring for disease or treatment sequelae often involves serial CBC, renal function testing (creatinine), urinalysis, C3 and C4, and laboratory tests monitoring specific drug toxicities, including homocysteine and cholesterol levels for patients taking corticosteroids.

Evidence Based Treatment Approaches

Current treatments for hepatitis C include ribavirin and pegylated interferon alpha. The use of interferon alpha is complicated by numerous well-known side effects, including early flulike symptoms, elevated triglycerides, gastrointestinal symptoms, dermato-logical disorders, and neuropsychiatric symptoms that include depressed mood, poor concentration, loss of appetite, fatigue, hostility, and suicidal ideation (Dieperink et al. 2000). Depression has been reported to develop in as many as 39 -45 of patients receiving interferon alpha (Capuron et al. 2003 Lotrich et al. 2007). Pegylated interferon, when compared with conventional interferon, does not protect against depression (Lotrich et al. 2007). The use of interferon alpha has also been associated with completed suicide (Fukunishi et al. 1998 Jans-sen et al. 1994). The risk of depression and suicidal ideation may continue after withdrawal from interferon alpha. Patients with hepatitis C should be monitored routinely for depressive...

Secondary Prevention of Stroke

The benefits of interventions sometimes go beyond the presumed mechanism of effect. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, called statins, reduce LDL-cholesterol and triglycerides and raise HDL-C to help decrease the risk from atherosclerosis, but also affect en-dothelial function. The primary benefit of the statins and gemfibrozil has been in stroke prevention in patients who have symptomatic coronary artery disease,41 but the benefit likely extends to patients at risk for atherothrombotic stroke or stroke associated with ischemic heart disease and aortic plaque. The angiotensin-converting enzyme inhibitors used for hypertension also lessen the risk for an arteriopathy. Exercise benefits many of the risk factors such as lipid, glucose, and blood pressure control, and may lower fibrinogen levels.

Understanding Your Blood Test Optimal Cardiac Numbers

We hear lots of numbers being tossed around when it comes to cardiovascular health. And without a clear understanding of each category, this information can be downright overwhelming. Key players include the cholesterol ratio, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, homocysteine, and your blood pressure score. Your HDL cholesterol, on the other hand, should not be too low. In fact, a low HDL cholesterol puts you at high risk for heart disease. HDL cholesterol that is less than 40 mg dL is considered low. Typically, a woman's HDL cholesterol ranges from 50-60 mg dL and a man's ranges from 40-50 mg dL. Triglyceride level is yet another reading. You want your triglyceride level to be under 150 mg dL, since high triglycerides can contribute to heart disease. If your triglyceride level is 150-199 mg dL, you are borderline-high, if it's 200-499 mg dL, it is high, and a reading of 500 mg dL is considered eoctremely high. The American Heart Association recommends...

Coronary Artery Disease

The cholesterol threshold for using statins in diabetic patients has been lowered to low-density lipoprotein (LDL) cholesterol greater than 100 mg dL, with a therapeutic target of 70 mg dL. A large statin trial has shown that patients who demonstrate elevated C-reactive protein (CRP) with normal LDL cholesterol values will benefit from statin therapy (Ridker et al., 2008). Many patients had metabolic syndrome with elevated triglycerides, which raises non-high-density lipoprotein (n-HDL) cholesterol, a risk lowered by statin therapy and more pathologic than LDL cholesterol. Aspirin may not be efficacious in all patients because of genetic factors. However, considering the relative safety of low-dose aspirin, many clinicians think the potential benefits outweigh a possible lack of efficacy. As noted, UKPDS showed that beta blockers and ACE inhibitors were equally effective in protecting the heart, brain, and kidney. Beta blockers are known to protect the previously injured heart but...

Extrarenal Macrovascular Disease

The renal arteries can be examined for stenosis using Doppler ultrasound. Magnetic resonance angiography (MRA) can provide high-resolution imaging of stenotic plaques and quality of the great vessels without the risks of contrast agents. Advances in endovascular surgery with stent placements have simplified renal artery repair and stabilized the aorta in the face of aneurysmal dilation and threatening rupture, which might be signaled by release of cholesterol-laden plaques. Early treatment with statins is thought to stabilize plaques and preclude devastating vascular complications.

The Metabolic Syndrome

The Adult Treatment Panel (ATP), in recommending guidelines for the treatment of hypercholesterolemia, defined the components of metabolic syndrome as any three of the following (NCEP ATP-III , 2002 Grundy et al., 2004a, 2004b) 3. Fasting serum triglycerides greater than 150 mg dL. 4. HDL cholesterol less than 40 mg dL in men and less than 50 mg dL in women. The Friedenwald equation is used to calculate the value of LDL cholesterol from the measured values of total and HDL cholesterol and triglycerides in the serum, as follows LDL cholesterol (Total cholesterol - HDL cholesterol) - (Triglycerides 5) Because high triglycerides would lower the calculated LDL cholesterol value, the ATP recommends treatment for non-HDL cholesterol (total cholesterol - HDL cholesterol) to a target of 130 mg dL or less. However, the diabetic, hypertensive, and coagulopathic disturbances of patients with metabolic syndrome also require intervention. Many drugs are needed to address these multiple risk...

Folic Acid Plus B6 and B12

Red rice yeast (cholestin) is currently being investigated as a way to lower cholesterol. With an ingredient called monacolin K that inhibits the production of cholesterol, red rice yeast looks promising as a food-based method of lowering LDL plaque. Red rice yeast also contains plant sterols, which may contribute to its cholesterol-reducing effects.

Plant Sterols or Stanols

You may know them as Take Control and Benecol. Whatever name they go by, these new margarine-like spreads may turn out to be promising weapons in the war against elevated total and LDL cholesterol levels. Plant sterol esters or stanol esters are natural substances found in wood pulp, leaves, nuts, vegetable oils, corn, rice, and some other plants. Now there is some evidence that the spreads (and salad dressings) made with plant sterols or stanols can actually reduce cholesterol absorption, and decrease the LDL cholesterol levels. For people trying to lose weight, light versions of these spreads are also available.

Genomics and Diet The Future

A woman in her early 60s is seen by a nutritional genomic counselor because she has had difficulty controlling her significantly elevated low-density lipoprotein (LDL) cholesterol level with diet and exercise. Several different statins were tried without effect. Her diet history reveals total fat intake less than 30 , polyunsaturated fatty acid (PUFA) intake near 5 , and monounsaturated fat intake as 17 of total energy intake. Her diet suggests appropriate fat intake, but her genome includes a polymorphism in the APOA1 gene. This polymorphism results in a low high-density lipoprotein (HDL) level when PUFA intake is low. She will need to increase her PUFA intake to improve her HDL as a protective effect against heart disease. She has a hepatic lipase gene that raises HDL when her fat intake is less than 30 of total energy. Her 3-hydroxy-3-methylglutaryl-CoA reductase gene has a variant that explains her poor response to statins in lower lipid levels. Lifestyle changes and keeping her...

RP Lifton FH Wilson KA Choate and DS Geller

Heart disease and stroke are the number one and number three leading causes of death in the United States, accounting for a third of all deaths annually. Epidemiologic studies have established a number of risk factors for these diseases, including hypertension, high cholesterol, diabetes mellitus, and smoking. Prospective randomized trials of blood pressure and cholesterol reduction and smoking cessation have established the causal relationship of these risk factors to disease, because modifying these parameters prevents adverse clinical outcomes, including death. In the case of cholesterol, initial therapeutic agents had modest cholesterol-lowering effects that reduced risk of heart attack but did not reduce overall mortality. Understanding the cholesterol biosynthetic pathway ultimately led to identification of rate-limiting steps in the pathway and development of highly potent cholesterol-lowering agents, the HMG-CoA reductase inhibitors. These agents lower cholesterol far more...

Mechanisms Of Arteriogenesis Versus Plaque Angiogenesis

The strategies employed in early therapeutic angiogen-esis trials tested the delivery of endothelial cell growth factors as single agents to augment collateral growth. These studies have been based on benefits shown in animal studies with porcine, rabbit, or canine models of myocardial and limb ischemia (Ware and Simons 1997). The structure of collateral vessels comprises several cell types (smooth muscle cells and endothelial cells), and growth of collaterals requires remodeling of the medial layer. The ability of a single endothelial cell growth factor to achieve collateral growth implies that this single agent activates or complements a cascade of cellular events in order to remodel a complex vascular structure with normal arterial and venous connections. Although single agents have shown promising results in preclinical studies on young adult animals, results in clinical trials have been less favorable in patients with significant atherosclerosis. A reduced arteriogenesis response...

Risk Factors for Stroke

Knowledge of stroke risk factors has advanced substantially during the past several decades and exceeds that of many other major neurological diseases. Important stroke risk factors include advanced age, systolic hypertension, diabetes mellitus, hypercholesterolemia, carotid artery stenosis, TIAs, cigarette smoking, lack of exercise, cardiovascular disease, atrial fibrillation, and left ventricular hypertrophy (LVH) on electrocardiography (ECG). y , y Based on epidemiological data, a risk profile table can be used to estimate a person's 10-year probability of stroke occurrence. y Stroke rates increase dramatically with age. About two thirds of all strokes occur after the age of 65. In the Framingham study the mean age of stroke patients was 65.4 years for men and 66.1 years for women. y As the population ages, the burden of stroke becomes greater.

Angiogenesis Will Stabilize Lesions

It is not yet determined whether therapies that directly inhibit or regress intimal vessels will result in lesion stabilization. The experimental verifications of these questions are partly limited by animal models of atherosclerosis that are widely accepted to represent plaque rupture and hemorrhage events in human disease, although some murine strains can manifest specific features (Palinski and Napoli 2002). In several animal models of atherosclerosis, lesion regression after withdrawal of an atherogenic diet is often accompanied by regression of in-timal vessels, decreased macrophages, reduced metallo-protease activities, and reduced intraplaque hemorrhage (Williams et al. 1988b Aikawa et al. 1998). Non-cholesterol-lowering doses of HMG-CoA reductase agents have anti-angiogenic effects and reduce plaque angiogenesis in vivo however, these properties may not account for the mechanisms of plaque stabilization observed in widespread clinical use (Park et al. 2002 Wilson et al. 2002)....

Subarachnoid Hemorrhage SAH

The incidence of SAH increases with age (mean age of approximately 50 years) and is higher in women than in men. Blacks are at higher risk than whites. Population-based mortality rates for SAH have progressively declined, and the survival rate after SAH has improved since the 1970s. The risk of SAH is increased during the third trimester of pregnancy. SAH due to aneurysm rupture is a leading cause of maternal mortality, contributing to between 6 and 25 percent of maternal deaths. Significant risk factors for SAH include smoking, hypertension, and heavy alcohol use. Use of oral contraceptives, hormone replacement therapy, hypercholesterolemia, and physical activity are not significantly related. During pregnancy, there is also a greater risk of AVM rupture y , y

Use Of Angiogenesis Stimulators Versus Inhibitors

Tors will activate angiogenesis in the plaque. On the other hand, ischemic myocardium and limbs also have increased expression of VEGF and bFGF, yet systemic delivery of these growth factors results in angiogenesis and the development of collateral vessels. Recent studies have shown atherosclerosis is enhanced after short-term exposure to endothelial cell stimulators (Celletti et al. 2001 Heeschen et al. 2001). Some of these effects of growth factors could be related to other actions of these agents and not be restricted to their effects on plaque an-giogenesis alone. Many angiogenic factors have effects on other cell types found within atherosclerotic lesions. For example, bFGF may promote smooth muscle cell proliferation and the growth of lesions independent of an effect on plaque capillaries. VEGF has effects on mono-cyte cells via the VEGF receptor 1 and may promote the release of endothelial or hematopoietic progenitor cells from the bone marrow that can migrate into...

Metabolism and body composition

In studies administering DHEA in physiological (25-50 mg day) or near physiological doses (100 mg day) a significant decrease in apolipoprotein A1 and HDL-cholesterol was seen in women but not in men (Diamond et al. 1996 Morales et al. 1994 1998). This corresponded to an increase in circulating androgen concentrations in women but not in men. In one study employing a dose of 100 mg day DHEA, a slight, but significant, HDL-cholesterol reduction was also seen in men (Flynn et al. 1999) who concurrently showed an increase in both free testosterone and 17 -estradiol serum concentrations.

SREBPs Transcriptional Mediators of Lipid Homeostasis JD Horton JL Goldstein and MS Brown

Sterol regulatory element-binding proteins (SREBPs) are a family of membrane-bound transcription factors that regulate cellular lipid synthesis and the clearance of atherogenic lipoproteins from the blood. They were initially isolated as proteins that transcriptionally regulated two genes involved in cholesterol homeostasis, the low-density lipoprotein (LDL) receptor, a transmembrane protein responsible for binding and internalizing LDL cholesterol from plasma, and 3-hydroxy-3-methylglu-taryl-coenzyme A (HMG-CoA) synthase, a key enzyme in the cholesterol biosynthesis pathway (Goldstein et al. 2002). Subsequent studies have revealed that SREBPs directly activate the expression of more than 30 genes dedicated to the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids, as well as the NADPH cofactor required to synthesize these molecules (Horton et al. 2002). In this paper, we will focus on the transcriptional activating properties of each SREBP family...

Function Of Srebps In Vivo

To bypass the embryonic lethality described above, tissue-specific knockout mice that lack all SREBPs in liver were produced using Cre LoxP technology. To generate these mice, loxP recombination sites were inserted into introns that flank key exons in the Scap or Sip genes (floxed alleles). Mice with the integrated floxed alleles were bred with transgenic mice expressing Cre recombi-nase under control of an interferon-inducible promoter (MX1-Cre). These mice were then injected with poly-inosinic acid-polycytidylic acid to induce the Cre recom-binase production in liver, which disrupts the floxed gene by recombination between the loxP sites. Cre-mediated deletion of Scap or Sip in the adult mouse liver resulted in dramatic reductions in the amounts of nSREBP-1 and nSREBP-2, and their associated target genes in both cholesterol and fatty acid synthetic pathways. As a result, the rates of cholesterol and fatty acid synthesis were reduced by 70-80 in livers of both the Scap- - and Sip-...

Srebp Expression And Plasma Lipid Levels

SREBPs clearly stimulate lipid synthesis, but they also enhance LDL receptor expression. These properties have opposing effects on plasma lipid levels, inasmuch as the final plasma lipid concentration ultimately depends on the balance between production and clearance (Brown and Goldstein 1997). Cholesterol and triglycerides are secreted from the liver in very-low-density lipoprotein (VLDL) particles. In most hepatocyte cell lines, VLDL production and secretion are tightly linked and positively associated with rates of cellular lipid synthesis. Transgenic mice that overexpress nSREBPs in liver have elevated rates of lipid synthesis however, as discussed in the preceding section, their plasma cholesterol and triglycerides are generally lower than those of wild-type mice (Horton et al. 2002). nSREBP-la and demonstrated that they secrete 10-fold more cholesterol and triglycerides in the form of VLDL than do hepatocytes isolated from wild-type mice (Hor-ton et al. 1999). The VLDL particles...

Checking data supplied

Plausibility checks should include range checks on variables supplied, asking the original investigators to confirm any extreme outliers or unusual values for example, confirming that records of unusually old or young patients or those with abnormally high or low cholesterol levels are indeed correct. Information supplied should also be checked against any relevant study publications, for example by confirming that the distribution of baseline characteristics, the number of participants and outcome results are consistent (bearing in mind that continued enrolment or additional follow-up may have altered information subsequent to publication).

Risk Factors for Depression

Some biological variables have been explored to determine their relationship with depression. An association between lower cholesterol level and a higher prevalence of depressive symptoms in middle-aged men has been reported (Steegmans et al., 2000), and there is evidence that serum cholesterol levels may be associated with variations in mental state or personality (Boston et al., 1996). Studies of the relationship between APOE genotype and depression have resulted in mixed findings. Krishnan et al. (1996) found an association between the APOE 3 and 4 alleles and late onset major depression. However, no association was observed between APOE genotype and change in depressive symptoms in a five-year longitudinal study of community-dwelling older adults (Mauricio et al., 2000). Similarly, depression was not strongly associated with APOE polymorphism in a sample of 806 persons aged 78 or older (Forsell et al., 1997).

Discussing Defense Mechanisms and Coping Styles

Patients may benefit from discussing their maladaptive defenses and coping styles and exploring ways of effectively dealing with their situation. For example, an obsessive-compulsive patient has a high cholesterol level and is calling the physician's office for more details about other laboratory tests. The results of the lipid profile are given to the patient, who now wants to know whether a lifestyle change or a statin medication would work better. With the recommendation for an initial lifestyle plan of more exercise and nutritional counseling, the patient becomes concerned about how to pay for this. Repeated efforts to help the patient with additional information are not making the patient feel any better. In fact, more information just raises more requests for additional information. The patient is asked to come for another visit. At this visit, the physician might say, I can continue to give you more information, but it seems that anxiety is driving your questions. What are you...

Cardiovascular surgeon See cardiac surgeon

Cholesterol ratio Ratio of the total cholesterol measured in the blood to the amount of high-density lipoproteins (HDL). A high ratio of total cholesterol to HDL-cholesterol usually indicates greater risk for having coronary disease or a more rapid progression of existing coronary artery disease.

Special Patient Considerations Ethical and Personal Beliefs

When assessing a patient for PN, attention should be given to patients with special personal dietary choices (e.g., vegetarians, vegans) or religious beliefs (e.g., Jehovah's Witness). These rare situations may present unique challenges for clinicians. Most nutrients used in PN preparations are usually from synthetic sources (e.g., crystalline amino acids) or vegetable sources (e.g., triglycerides used in IV lipid emulsions), with the only exception usually being egg phospholipids used in IV lipid emulsions. Discuss these issues for patients with specific needs who require PN so that a plan can be developed to provide appropriate nutrition support therapy.

What do you do now

This patient has developed strokes and encephalopathy related to cardiac surgery. Haloperidol use likely adds to his encephalopathy and should be stopped. Haloperidol is very slowly removed from the circulation. Its use substantially delays recovery. When patients develop rebound hyperactivity on withdrawing from haloperidol, physicians unfortunately often prescribe an even higher dose. In my opinion haloperidol should never be used in older patients, especially in those with neurological abnormalities. The one indication is hemiballism when other measures do not control the violent motions. Cessation of statins can lead to a rebound increase in the likelihood of cardiac and brain ischemic events. I prescribed beginning again atorvastatin 80 mg day given through his nasogastric tube.

Therapeutic Strategies to Decrease ROS Production in the Penis

Continued research in the area of improving erectile function in disease states is pointing to the greater importance of targeting ROS formation, rather than ROS scavenging, for the development of an effective therapeutic strategy to reduce oxi-dative damage in the penis and ED. Several pharmacological agents have been suggested to inhibit ROS production and improve erectile function through mechanisms different and beyond their primary therapeutic actions, such as PDE5 inhibitors, angiotensin-converting enzyme (ACE) inhibitors and ATj receptor antagonists, statins, and BH4. This type of therapeutic strategy falls within the first line of recommended treatment of ED. This line of intervention involves preventable lifestyle modifications (such as discontinuation of cigarette smoking, exercise and weight control, Mediterranean-style diet, and a reduction in caloric intake) and treatable noninvasive pharmacologic therapies.

Patient Encounter 2 Part 2 PMH Obesity and acne

FH Father is living and has hypertension. Mother is living and has diabetes mellitus and hypercholesterolemia. Both parents are obese. Labs Urine HCG negative, free testosterone 100 ng dL (3.47 nmol L) (elevated), TSH 2.1 pU mL (2.1 mU L) (within normal limits), prolactin 9 ng mL (9 mcg L) (within normal limits), fasting glucose 120 mg dL (6.66 mmol L). Fasting lipid panel Total cholesterol 181 mg dL (4.69 mmol L), HDL cholesterol 58 mg dL (1.50 mmol L), triglycerides 65 mg dL (0.73 mmol L), LDL cholesterol 110 mg dL (2.85 mmol L)

Sequelae of Hypothyroidism

Hypothyroidism is a chronic disease that may result in significant long-term sequelae. Hypercholesterolemia is associated with hypothyroidism, increasing the long-term risk of cardiovascular disease and cardiovascular mortality.14 Between 4 and 14 of patients with hypercholesterolemia are found to be hypothyroid. The Colorado Thyroid Health Study showed a direct correlation between the degree of TSH elevation and the rise in serum cholesterol. Hypothyroidism also may result in increased systemic vascular resistance, decreased cardiac output, and increased diastolic blood pressure. Hypothyroidism can cause significant neuropsychiatric problems, including a dementia-like state in the elderly that is reversible with LT4 therapy. Maternal hypothyroidism can have dire consequences for the developing fetus. The fetus is almost completely dependent on maternal thyroid hormones during the first trimester, a time crucial for development of the CNS. Inadequately treated maternal hypothyroidism...

Biomedical Demography

Demographers over the past half century have increasingly become involved with the design of surveys and the analysis of survey data, especially pertaining to fertility or morbidity and mortality. Recently, various kinds of physical measurements (height and weight), physiological measurements (of blood pressure and cholesterol levels), nutritional status (assessed by the analysis of blood or urine and other methods), physical performance (hand-grip strength or ability to pick a coin up from the floor), and genetic makeup (as determined by analysis of DNA) have been added to surveys, including those conducted by Christensen, Goldman, Weinstein, Zeng, and others. Such biological measurements can be used as covariates in demographic analyses in much the same way that social and economic information is used. These kinds of analyses are an important activity of biomedical demographers (Finch et al. 2000).

Patient Encounter 2

LC is a 51-year-old female with a history of CHD (stent placement in the left anterior descending coronary artery 3 years prior) and type 2 diabetes who is referred to you for follow-up of her cholesterol. She is taking simvastatin 20 mg once daily in the evening for her cholesterol, metformin 2,000 mg once daily in the evening, and pioglitizone 15 mg once daily for diabetes. Her diabetes is well controlled. Her laboratory test results are within normal limits, except for her fasting lipid profile total cholesterol 215 mg dL (5.57 mmol L), triglycerides 135 mg dL (1.53 mmol L), HDL cholesterol 51 mg dL (1.32 mmol L), and LDL cholesterol 137 mg dL (3.55 mmol L). Bile Acid Sequestrants Cholestyramine, colestipol, and colesevelam are the bile acid-binding resins or sequestrants (BAS) currently available in the United States. Resins are highly charged molecules that bind to bile acids (which are produced from cholesterol) in the gut. The resin-bile acid complex is then excreted in the...

Targeting Nadph Oxidase 281011 PDE5 Inhibitors

28.10.1.3 Statins (3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors) Beneficial pleiotropic effects of statins are due to the improvement of endothelial function at least in part by reducing oxidative stress and improving eNOS function independent from their cholesterol-lowering effect. Statins upregulate antioxi-dants SOD3 and catalase 150, 151 and inhibit endothelial superoxide formation. The latter effect is due to the inhibition of NADPH oxidase 152 and eNOS uncoupling 153 , Basic science studies demonstrate that several statins, such as rosuvastatin and atorvastatin, improve diabetes- 154, 155 , metabolic syndrome- 156 , and hypertension- 157 related ED and increase the responsiveness to sildenafil by inhibiting RhoA ROCK signaling in the penis. A limited number of clinical studies which evaluated the effect of statin therapy in men with ED have produced mixed results. Some 158-162 , but not all 163, 164 , studies demonstrated a beneficial effect of atorvastatin on...

Regulation Of Srebp Isoform Expression

Plasma Fplc

As discussed above, SREBP-lc stimulates two enzymes required for the synthesis of polyunsaturated fatty acids. Polyunsaturated fatty acids also mediate a negative-feedback loop that suppresses SREBP-lc expression and lipogenesis. LXR-mediated regulation of SREBP-lc appears to be one mechanism by which SREBP-lc transcription and fatty acid synthesis are suppressed by polyunsaturated fatty acids. In vitro, unsaturated fatty acids competitively block LXR activation of SREBP-lc transcription by antagonizing the activation of LXR by its endogenous ligands (Ou et al. 200l). In vivo, rodents fed diets containing polyunsaturated fatty acids have reduced SREBP-lc levels and low rates of lipogenesis in liver (Xu et al. l999). In addition to LXR-mediated transcriptional inhibition, polyunsaturated fatty acids lower SREBP-lc expression by accelerating degradation of its mRNA (Xu et al. 200l). These combined effects result in decreased SREBP-lc expression, which may contribute to the ability of...

Arh Is Required For Ldlr Internalization

Analysis of a large collection of Sardinian patients with ARH indicated that the mean plasma levels of LDL cholesterol are lower in these patients than in patients with homozygous FH (Arca et al. 2002). Approximately half of the Sardinian ARH patients had evidence of coronary artery disease at the time of diagnosis, and six of these patients were below the age of 40. Thus, the elevated plasma cholesterol levels in ARH patients are clearly associated with premature coronary artery disease. However, the onset of disease tends to be later in ARH patients than in patients with homozygous FH. Although patients with ARH have somewhat lower plasma cholesterol levels and delayed onset of coronary atherosclerosis compared to FH homozygotes, they tend to have large xanthomas. The LDLR is not thought to play a direct role in the formation of cholesterol-rich foam cells, since the LDLR is expressed at very low levels in cholesterol-loaded macrophages (Goldstein et al. 2001). However, studies in...

Overview of Glucose Metabolism

In the postprandial phase, insulin-requiring glucose disposal occurs in many body tissues, most prominently in the liver and muscle. After nutrient ingestion, insulin secretion is stimulated directly by a rise in both plasma glucose and amino acids and indirectly through the action of a variety of incretins, or intestinal factors that promote insulin secretion.3 In liver and muscle, insulin stimulates storage of glucose into glycogen and amino acids into protein. In adipose tissue, insulin stimulates free fatty acid (FFA) incorporation into triglycerides (TGs). Insulin action is balanced by the effects of counter-regulatory hormones, most notably glucagon and catecholamines.24 Both hormones stimulate hepatic glycogenolysis and gluconeogenesis in the liver, whereas catecholamines have additional effects on the pancreas to inhibit insulin release and on muscle to inhibit insulin action. In the postabsorptive or fasting phase, the liver becomes an organ of net glucose production...

Step 1 Patient Assessment

Determine lipoprotein profile after fasting for 9 to 12 hours. The NCEP guidelines recommend that all adults greater than 20 years of age should be screened at least every5 years using a fasting blood sample to obtain a lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides). A fasting lipid profile is preferred so an accurate assessment of LDL cholesterol can be performed. Fasting permits the clearance of triglycerides carried by chylomicrons from the circulation, thus allowing VLDL cholesterol to be determined. Children between 2 and 20 years old should be screened for high cholesterol if their parents have premature CHD or if one of their parents has a total cholesterol greater than 240 mg dL (6.22 mmol L).3 Early screening will help to identify children at highest risk of developing CHD, in whom early education and dietary intervention is warranted.

Hematocrit and ischemic disease

Further adverse parameters can lower the critical threshold of hematocrit down to even 41 . Ischemic lesions were predominantly located in deep subcortical structures where artery calibers are small (Tohgi et al. 1978). In a later study, the critical threshold of hematocrit was seen to be higher (> 50 ) in an analysis of 320 patients suffering mortal cerebral ischemia (Lowe etal. 1983). A prospective study, which surveyed over 1000 residents during a 16-year period in regard to cerebral ischemic events, revealed increased hematocrit (> 45 ), also after correction for arterial hypertension and age, as independent risk factor (Kiyohara et al. 1986). Such results are confirmed by another prospective study involving 1000 patients identifiable risk factors present in these stroke patients were arterial hypertension (64.3 ), smoking (35.2 ), diabetes mellitus (26.9 ), hypercholesterolemia (24.1 ), high hematocrit (> or 50 ) in 21.8 and a clinically identified potential cardiac sources...

Commercial Antioxidants

Several beverages, such as pomegranate juice, red wine, blueberry juice, cranberry juice, orange juice, and green tea, have been touted to have roles in improving erectile function in disease states via their ROS scavenging capacities. In animal models of arteriogenic ED, pomegranate juice decreased oxidative stress and improved, although it did not normalize, erectile function 171, 172 . This beneficial effect of pomegranate juice may be due to its main active ingredients such as polyphenol antioxidants. The other natural polyphenol, resveratrol, found mostly in grapes and red wine, restores penile function in animal models of hypercholesterolemia 173 - and diabetes 174 -induced ED. Cardiovascular protective effects of resvera-trol have been attributed to activation of eNOS and the improvement of endothelial function 175 . However, the exact role and mechanism of action of these commercial antioxidants on oxidative stress in the penis and erectile function await further basic science...

Kush Singh and Clyde A Helms

Achilles Tendon Mri Section Images

Several different clinical scenarios warrant evaluation of the Achilles tendon with magnetic resonance imaging (MRI). However, the main reasons to image the Achilles are pain, trauma, infection, or a mass. Less commonly, an MRI may be used to screen for hypercholesterolemia. Although a diagnosis of Achilles tendon rupture is usually evident clinically, the gap between the ruptured ends of the tendon may be difficult to ascertain by physical examination alone. This gap is frequently used to determine which technique will be employed for surgical repair. When the gap is small, and the injury acute, then nonoperative management may be selected (see Chapter 5). In the chronic rupture, when the gap is less than 6 cm, the augmentation techniques can be applied and when the gap is greater than 6 cm, then tendon transfer is selected. It is often useful for the surgeon to know which technique will be best utilized for preoperative planning, and in these situations MRI can be quite helpful....

Sitosterolemia Is A Disorder Of Neutral Sterol Trafficking

Forms of hypercholesterolemia in three important aspects. First, patients with sitosterolemia have markedly increased concentrations of plant sterols, as well as animal-derived sterols, in their blood and body tissues (Bhat-tacharyya and Connor 1974). Whereas the plasma concentrations of sitosterol and campesterol, the major plant sterols, almost invariably constitute less than 1 of the circulating sterols in normal individuals, they can exceed 20 of the plasma sterols in sitosterolemic patients (Salen et al. 1992). Neutral sterols also accumulate in the tissues of sitosterolemic patients in proportion to their concentrations in the circulation (Salen et al. 1985). Second, the plasma cholesterol concentrations of sitos-terolemic individuals are remarkably sensitive to dietary cholesterol intakes. For example, Belamarich et al. (1990) reported that the plasma cholesterol levels of an 11-year-old sitosterolemic patient decreased from 444 mg dl to 177 mg dl after 3 months on a...

Surgical complications

Transection of major lymphatics, particularly those that drain directly into the cisterna chyli, may result in formation of chylous ascites in around 2 of patients undergoing RPLND 40 . This lymphatic fluid can cause abdominal distention, diaphragmatic irritation, and dyspnea within weeks of surgery. The diagnosis of chylous ascites is confirmed with paracentesis. Treatment strategies include low-fat diets supplemented with medium-chain triglycerides that circumvent small bowel absorption. If these conservative dietary changes are ineffective, IV hyperalimentation is used with or without the somatostatin analogue octreotide 41 . Finally, surgical exploration and ligation or the creation of peritoneovenous shunts may become necessary for recalcitrant cases 33 .

Kayser Fleischer Ring

Kayser Fleischer Ring

A whitish ring at the perimeter of the cornea is probably an arcus senilis. In patients older than 40 years, this finding is usually a normal phenomenon. Although there are many false-positive findings, patients younger than 40 years may have hypercholesterolemia. An arcus senilis is seen in Figures 10-53 and 10-54.

Effects of exogenous testosterone on cardiovascular risk factors

In the majority of studies, substitution of testosterone in hypogonadal men had no impact on total cholesterol, LDL cholesterol and triglycerides but decreased HDL-C and Lp(a) levels. those seen in men. On the one hand, insulin sensitivity contributes to the patho-genesis of hyperandrogenemia in polycystic ovary syndrome. Insulin stimulates androgen synthesis in the ovaries via its cognate receptor and the inositolglycan pathway (Nestler et al. 1998). Since the ovaries remain sensitive to insulin when other tissues such as fat and muscle are resistant, hyperinsulinemia can augment the LH-dependent hyperandrogenism in insulin resistant women with polycystic ovary syndrome (Dunaif and Thomas 2001). In support of this, treatment of insulin resistance in women with polycystic ovary syndrome with metformin or the insulin sensitizer troglitazone significantly decreased serum levels of insulin as well as testosterone, independently of body mass index or gonadotropin levels (Kolodziejczyk et...

Nox Family of Nadph Oxidases

NADPH oxidases are activated by diverse stimuli such as angiotensin II, proinflammatory cytokines, vasoconstrictors, hypoxia, growth factors, metabolic factors (hyperglycemia, hyperinsulinemia, free fatty acids, advanced glycation end products AGEs ), mechanical stimuli, and superoxide itself. The NADPH oxidase-derived ROS have been implicated in aging and a variety of diseases, including hypertension, diabetes mellitus, hypercholesterolemia, hypertension, and SCD 19 . In recent years, emerging evidence suggests a role of NADPH oxidase in several ED states, as discussed later in this chapter.

Morbidity of retroperitoneal lymph node dissection after chemotherapy

Injury to lymphatic channels, resulting in chylous ascites, occurs in 2 of cases 23 . Factors that predispose to this complication include suprahilar dissection, liver resection, or resection of the inferior vena cava. Dietary manipulation with medium-chain triglycerides and diuretic therapy are the mainstays of management. Lympho-celes may also result from the lymphatic injury, and percutaneous drainage is necessary if there is superimposed infection, hydronephrosis, or prolonged ileus. Injury to the inferior vena cava or aorta may necessitate primary repair or the use of interposition grafts, and injury to renal vessels may occur, resulting in renal infarction and loss of the kidney. Spinal cord ischemia is rare and is usually associated with advancing age and dissection around the anterior spinal artery near the T8 level. Small bowel obstruction is present in 2 and often responds to conservative measures 23 . Prolonged ileus may mask underlying pancreatitis, retroperitoneal...

Hyperviscosity and low flow

A 65-year-old with hypercholesterolemia was referred to the hospitalbecause of a sudden weakness of left face, arm and leg. He was unable to walk. He was dysarthria Symptoms disappeared after about 10 minutes but over the next 5 hours he had four further identicalepisodes lasting for severalminutes. The next day he suffered a lacunar stroke in the internalcapsule with persisting pure motor hemiparesis. It is assumed that the occlusion of a single perforating artery (lenticulostriate artery) was the cause of the lacunar infarct. Figure 9.3. Capsular warning sign. A 65-year-old with hypercholesterolemia was referred to the hospitalbecause of a sudden weakness of left face, arm and leg. He was unable to walk. He was dysarthria Symptoms disappeared after about 10 minutes but over the next 5 hours he had four further identicalepisodes lasting for severalminutes. The next day he suffered a lacunar stroke in the internalcapsule with persisting pure motor...

Niacin and Nicotinic Acid

Superphysiological doses of niacin (1.5 to 3 g daily) have been used successfully in the treatment of hypercholesterolemia, and this practice diminishes mortality by reducing a coronary artery disease risk factor. Side effects of high-dose niacin include flushing, hyperuricemia, hyperglycemia, and elevations in liver enzymes.

Revascularization and Outcomes in the Symptomatic Patient

There are important limitations in extrapolating these results to modern practice. Medical therapy was inconsistent and limited to P-blockers, digoxin, diuretics, and aspirin (used in only 20 of the medical arm). There were no statins or angiotensin-converting enzyme (ACE) inhibitors, and calcium antagonists were largely absent. There was a 30 crossover rate to bypass and very limited use of arterial conduits. Although 2649 patients with stable angina were included, only 85 were women, and few were older than 65 years.23 Despite these limitations, these data serve as a basis for the following discussion.

Hypertension smoking alcohol cholesterol and drugs

While elevated cholesterol levels play a less significant role in ICH than in ischemia, statin use and or very low levels of cholesterol have been questionable factors in increasing the risk of ICH. In one series of 629 ICH patients the effect of statin use was investigated. Statins were used by 149 629 (24 ) before ICH. There was no effect of pre-ICH statin use on the rates of functional independence (28 versus 29 , P 0.84) or mortality (46 versus 45 , P 0.93). Conversely, ICH survivors treated with statins after discharge did not have a higher risk of recurrence (adjusted HR 0.82, 95 CI 0.34-1.99, P 0.66). Thus, inferences made from observational data show that statin use prior to ICH does not influence mortality or functional outcome and statin use following

Pathophysiology Lipid and Lipoprotein Metabolism

Lipoprotein Structure

Cholesterol is an essential substance manufactured by most cells in the body. Cholesterol is used to maintain cell wall integrity and for the biosynthesis of bile acids and steroid hormones. Other major lipids in our body are triglycerides and phospholip-ids. Since cholesterol is a relatively water-insoluble molecule, it is unable to circulate through the blood alone. Cholesterol along with triglycerides and phospholipids are packaged in a large carrier-protein called a lipoprotein (Fig. 12-1). Lipoproteins are water soluble, which allows transportation of the major lipids in the blood. These lipoproteins are spherical and vary in size (approximately 1,000 to 6 nm) and density (less than 0.94 to 1.21 g mL) (Table 12-1). The amount of cholesterol and triglycerides vary by lipoprotein size. The major lipoproteins in descending size and ascending density are chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and...

Table 305 Glycogenoses

These diagnoses can usually be made by performing assays of enzymatic activity in the particular tissue most affected, such as the liver, peripheral white cells, muscle, and even brain. Since severe hypoglycemia is the best screening indicator of this class of disease, postprandial and glucose tolerance tests are particularly useful. A variety of other biochemical tests, such as uric acid, cholesterol, fatty acids, triglycerides, lipid profiles, and liver function tests, should be performed, as well as bone studies in specific instances. Management, Prognosis, and Future Perspectives. Therapy varies depending on the particular syndrome involved. In Von Gierke's disease, small amounts of free glucose can be given to maintain normal glucose concentrations dietary carbohydrates are also given, but because excessive glucose leads to glycogen storage in the liver and kidneys, small feedings of carbohydrates are the preferred method of treatment. Dietary substitution of medium-...

Abcg5 And Abcg8 Promote Neutral Sterol Excretion Into Bile

The specific defects in sterol transport observed in sitosterolemic patients indicate that ABCG5 and ABCG8 facilitate the excretion of sterols from the liver and intestine. To test this hypothesis, we developed P1 transgenic mice expressing human ABCG5 and ABCG8 (Yu et al. 2002). The transgenes were expressed primarily in the liver and small intestine, mirroring the tissue distribution of expression of the endogenous genes. Transgene expression had only modest effects on plasma and liver cholesterol levels, but biliary cholesterol levels were increased more than fivefold compared to wild-type mice. This finding demonstrates that biliary secretion of cholesterol can be driven by increased expression of ABCG5 and ABCG8, leading to a compensatory increase in cholesterol synthesis and a selective increase in fecal neutral sterol excretion. The fractional absorption of dietary cholesterol was reduced 50 in the transgenic mice (Yu et al. 2002). Biliary phospholipid concentrations were...

Polycystic Ovary Syndrome

In the long-term management of PCOS, steps should be taken to reduce cardiovascular complications, diabetes, obesity, and psychosocial morbidities (Fig. 35-8). Screening for glucose-intolerance with a 75-g 2-hour FTT and determination of serum lipid levels (total cholesterol, LDL, HDL, triglycerides) should be carried out. Lifestyle management changes include weight loss, exercise, and use of metformin and thiazolidinediones for patients with abnormal GTT results. In addition, clinicians should consider cardiovascular risk reduction, psychosocial issues, management of subfertility and hirsutism, and other lifetime management with insulin sensitizers and protection of the endometrium with hormonal manipulations.

Patient Care and Monitoring

Determine the treatment goal for LDL cholesterol based on the patient's CHD risk and non-HDL cholesterol goal if patient meets criteria for metabolic syndrome. For patients exceeding their LDL cholesterol goal, initiate TLCs. Consider starting concurrent pharmacotherapy in patients in the high-risk or moderately high-risk categories. Pharmacotherapy should be initiated at a dose to reduce LDL cholesterol by 30 to 40 at a minimum. Once the LDL cholesterol goal is achieved, assess non-HDL cholesterol in those with metabolic syndrome and intensify LDL-lowering therapy further or consider adding niacin or fibrate.

Arterial Dolichoectasia with Pontine Infarction

Noncontrast brain CT did not show an infarct or hemorrhage. MRI of the brain showed an acute small infarct involving the left pontine base on diffusion-weighted imaging. MRA of the brain and neck without contrast showed an ectatic basilar artery that deviated to the left and compressed the left trigeminal nerve. The mid-basilar artery was 30 stenosed. Transthoracic echocardiogram did not show a cardioembolic source. Telemetry did not reveal any arrythmias. Fasting lipid panel revealed total cholesterol 220 mg dl, LDL 160 mg dl, triglycerides 250 mg dl, and HDL 40 mg dl. The patient was started on aspirin 325mg daily and simvastatin was increased to 80mg qhs. For the trigeminal neuralgia, he was given trileptal 150 mg bid that was increased to 300 mg bid two weeks later.

Followup of Health Survey Detected Hypercalcemia

Using national registration numbers and the causes of death registry, survival was compared between individuals who were hypercalcemic at the 1969 to 1971 survey and matched normocalcemic control subjects.23 Survival during the 14-year follow-up was significantly lower among the hypercalcemic individuals.23 The difference in survival steadily increased and became more marked after 5 years from the initial health survey.23 The hypercalcemic individuals also had significantly higher diastolic and systolic blood pressures as well as serum uric acid and a tendency toward higher glucose and cholesterol levels. Using multivariate analyses, higher levels of serum calcium were associated with increased mortality in patients older than 60 years, but this effect diminished in the oldest age groups. Life table analyses revealed a significant difference in survival between hypercalcemic persons and control subjects at age 70 or younger but not for those older than 70 years (Fig. 41-2).23 The...

Chronic infections and stroke

Atherosclerosis is a common disease and a major risk factor for stroke. Its etiology can largely be explained by the classic risk factors (age, gender, genetic predisposition, hypertension, diabetes, hypercholesterolemia, diet, smoking, low physical activity, etc.). Additionally, pathogens such as Helicobacter pylori, cytomegalovirus, herpes simplex virus and Chlamydia pneumoniae have been proposed to be associated with atherosclerosis.

Physiology and Pharmacology

Several states, such as pregnancy, malabsorption, and caloric deprivation, and certain drugs alter levothyroxine needs, and these are of particular importance when supraphysiologic dosing is required (Table 8-1). During pregnancy, serum TSH levels increase largely as a result of an increase in T4-binding globulins, with a consequent fall in circulating free T4 and free T3. This is offset by a natural amelioration of such diseases as chronic autoimmune thyroiditis but, in general, T4 requirements tend to be greater.3940 Certain drugs may block T4 absorption (e.g., cholestyramine,41 sucralfate,42 aluminum hydroxide,43 ferrous sulfate44), increase nondeiodinative T4 clearance by pathways not leading to T3 generation, such as Cholestyramine41

Conditions that Affect the Maintenance Dose of T4

Several conditions require increasing the dose of T4. Pregnancy is the most important because more T4 is needed during pregnancy in patients with hypothyroidism based on serial serum TSH measurements.77 Similarly, patients with hypothyroidism who take estrogen require more thyroid hormone due to increased thyroid-binding protein by estrogen and subsequent decrease in available FT4.78 Medications to decrease T4 absorption include cholestyramine, sucralfate, ferrous sulfate, aluminum hydroxide, and calcium carbonate.79,80 Increased thyroid hormone replacement should be considered if patients are on these medications. Patients should also take these medications at a different time than when they take their thyroid hormone. Measurement of serum TSH levels is an excellent method to determine the appropriate T4 dose in patients with primary hypothyroidism. In contrast, some conditions require decreased thyroid hormone dose. Androgen therapy decreases T4-binding globulin and increases FT4...

The Goal of Evaluation

Subclinical Cushing

Garrapa and colleagues13 evaluated body composition and fat distribution, as measured by dual-energy x-ray absorptiometry (DEXA), in women with nonfunctioning clinically inapparent adrenal masses and in women with Cushing's syndrome compared with healthy controls matched for age, menopausal status, and body mass index. Women with clinically inapparent adrenal masses had larger waist circumference, reflecting intra-abdominal fat. The blood pressure was higher in patients with these tumors than controls, and 50 of patients were hypertensive. High-density lipoprotein (HDL) cholesterol levels and triglyceride mean values were also higher in patients with clinically inapparent adrenal masses than in controls. If central fat deposition, hypertension, and low HDL are important risk factors for cardiovascular disease, then patients with clinically inapparent adrenal masses, whether subclinically functioning or nonfunctioning, are at higher risk than the general population for cardiovascular...

Definition and Pathogenesis

Dyslipidemias implicated in the acceleration of atherogen-esis in the diabetic state. When fatty acids packaged into triglycerides are not properly degraded in tissues, their intracellular accumulation causes lipotoxicity, which in turn impairs cellular function, including the beta cell of the pancreatic islets.

Clinical implications

Some clinicians argue that androgen replacement in the elderly male, in addition to possible benefits on muscle, bone, sexual and mental functions, has the potential to prevent atherosclerotic vessel diseases. However, androgens have such an extraordinary array of effects in vivo that it is hazardous to extrapolate isolated experimental findings to the wider clinical setting. It is premature to assume clinical benefits from manipulation of the sex steroid milieu based on biologically plausible mechanisms, or indeed on cross-sectional risk factor observational data in a complex multifactorial condition such as coronary artery disease. Interpretations of effects of pharmacological doses of androgens on arterial compliance and flow-mediated dilatation in particular must also be treated with circumspection. The lessons from estrogen hormone replacement in postmenopausal women are especially salutary. Despite the overwhelmingly positive but indirect evidence on risk factors and disease...

Variation in the androgen receptor

A variable number of CAG repeats in exon 1 of the androgen receptor gene on the X-chromosome, which normally ranges between 9 and 35 encodes for a variable number of glutamine residues in the aminoterminal domain of the receptor and is inversely associated with the transcriptional activity of testosterone-responsive target genes. Abnormal expansion of the CAG repeats beyond the number of 36 leads to Kennedy disease, which is accompanied by signs of hypoandrogenism (see Chapter 2 for details). Within the physiological range of 9 to 35, the number of CAG repeats was shown to be inversely associated with the risk of prostate cancer, benign prostatic hyperplasia, sperm production, and bone density, and depression (Dowsing et al. 1999 Ferro et al. 2002 Seidmann et al. 2001 von Eckardstein et al. 2001 Zitzmann et al. 2001a). With respect to cardiovascular disease it is important to emphasize that the number of CAG repeats is positively correlated with flow-mediated vasoreactivity and...

Androstenedione administration in clinical studies

Effects of oral androstenedione have not been studied in women and have been largely disappointing in men. Short-term (5 days) androstenedione (100 mg day) had no anabolic effect on muscle protein metabolism in eugonadal young men (Rasmussen etal. 2000). In 30-56 year-old men androstenedione (3 x 100 mg day) for 28 days slightly reduced HDL-cholesterol without affecting prostate specific antigen (PSA), suggesting some androgenic activity (Brown et al. 2000). Serum HDL-cholesterol was also reduced in an eight-week randomized trial in 20 young men receiving oral androstenedione (300 mg day) (King etal. 1999). Androstene-dione failed to enhance muscle adaptation to resistance training in this population (King etal. 1999).

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